Case Report: Vertical muscle-sparing latissimus dorsi flap in the reconstruction of chronic radiation-induced chest wall ulcers after breast cancer surgery: a case series.

Introduction: Radiation therapy, a standard postoperative treatment for breast cancer, can lead to chronic ulcers owing to compromised tissue healing. Accordingly, flap surgery using healthy tissues is essential for aesthetic and functional recovery. Although various flap techniques exist, each has its own drawbacks. This study introduces the vertical muscle-sparing latissimus dorsi flap as a superior alternative due to its comparative operative efficiency and tissue preservation. Case report: Two female patients aged 60 and 59 years with histories of breast cancer in their left breast treated with radiotherapy presented with chronic ulcers. The first patient had a 4 × 5 cm defect infiltrating the pleural space, while the second had a 15 × 9 cm defect after thoracic surgery for a bronchopleural fistula. In both cases, debridement was followed by reconstruction using a vertical muscle-sparing latissimus dorsi flap, thereby avoiding the need to change the patient's position and repeated draping during surgery. Both patients showed good postoperative recovery without significant complications. Results: The vertical muscle-sparing latissimus dorsi flap resulted in better adhesions and functional outcomes due to shorter surgical duration. Conclusion: The vertical muscle-sparing latissimus dorsi flap is an effective and efficient method for reconstructing radiation-induced chest wall ulcers in patients with breast cancer. Its application in the presented cases highlights its potential as a preferred option in similar clinical scenarios.

Core contents for a menopausal health literacy intervention for South Korean middle-aged women: an e-Delphi study.

BACKGROUND: The attention on improving health literacy (HL) for self-management at the population level in many countries has been increasing. Although self-management among middle-aged women in the menopausal transition are important public health issues, few studies have developed the menopausal HL intervention reflecting the multidimensional aspects of HL. We aimed to generate consensus from an expert panel on the core contents of the menopausal HL intervention for middle-aged women based on the HL conceptual framework of the European Health Literacy Survey. METHODS: The panel comprised 20 experts from multiple disciplines (nursing, medicine, public health, and food and nutrition). We conducted the e-Delphi process in three rounds, asking the panel to evaluate and prioritize the appropriateness of the core contents and provide open-ended responses to additional comments about the menopausal HL intervention. The e-Delphi questionnaire was developed based on the HL framework, integrating health and HL domains. RESULTS: The experts reached a consensus on 38 components of the intervention. Among the 19 components of the four health domains, health topics in healthcare and disease prevention were more appropriate than those in health promotion. For the 19 HL competency components, strengthening the ability to access, appraise, and apply health information was more important than strengthening the ability to understand information. Finally, a consensus was achieved on the 12 priorities for intervention content by HL domains integrated with health domains. For example, contents included proper access to reliable information resources, understanding the definition and process of menopause, judging abnormal health symptoms, and performing the health checkups necessary for menopausal women. CONCLUSIONS: Our findings provide evidence for HL skills that nurses and other health professionals can consider when developing interventions to improve self-management among middle-aged women. Future research should focus on incorporating the core contents of multidimensional HL skills into menopausal HL interventions to improve self-management among middle-aged women.

A scintillating-fiber detector for making high-time-resolution secondary D-T neutron measurements in KSTAR.

A scintillating fiber (Sci-Fi) detector for the middle neutron flux range was installed in KSTAR as part of a collaboration between the National Institute for Fusion Science and the Korea Institute of Fusion Energy. The detector could make relatively high-time-resolution measurements of secondary deuterium (D)-tritium (T) neutron fluxes to investigate the degradation of D-D-born triton confinement, which is crucial for demonstrating alpha particle confinement, particularly above 0.9 MA in KSTAR. The pulse-height spectrum of the Sci-Fi detector exhibited two peaks, the higher of which corresponded to D-T neutrons. A discrimination technique was applied to extract the D-T neutron signal, revealing the time evolution of the D-T neutron flux during relatively high plasma current discharges with a 50 ms temporal resolution. Future research will involve investigating the causes of the degradation of the triton burnup ratio above 0.9 MA in KSTAR.

Validity and reliability of the Korean version of the Digital Burnout Scale.

Objectives: To investigate the factor structure and verify the validity and reliability of the Korean version of the Digital Burnout Scale (DBS) among Generation Z university students. Methodology: The World Health Organization guidelines were employed in the forward and back translation, synthesis, cross-cultural adaptation, and pre-survey phases to result in the Korean version of the DBS. The Korean version was then used to collect data from 330 university students online. Construct, convergent, discriminant, and concurrent validity, and internal consistency were assessed. Findings: The Korean version of the DBS had three subscales (digital aging, digital deprivation, and emotional exhaustion) and included 24 items. The results of the confirmatory factor analysis indicated adequate model fit indices. Convergent, discriminant, and concurrent validity were satisfactory. The Cronbach's ⍺ for the overall scale was 0.95. Conclusion: The Korean version of the DBS has good reliability and validity and can be used as a tool to assess the level of risk of digital burnout and provide appropriate support and intervention. Implications: The Korean version of the DBS will serve as a framework for developing healthy digital education by grasping individual characteristics. Longitudinal research is recommended to identify factors that cause digital usage and burnout for various age groups.

Effectiveness synchronous e-learning in nursing education: A meta-analysis and subgroup analysis.

AIM: This study aimed to identify the best available evidence of the effects of synchronous e-learning in nursing education through a meta-analysis and to compare mean effect sizes between study subgroups. BACKGROUND: With the rapid development of synchronous e-learning, adequate preparation is essential, as the formulation of effective educational strategies is crucial for learners' success. However, rather than focusing solely on using technology to implement e-learning, instructors should design education programs that meet learning objectives while considering appropriate technologies and types of interactions. DESIGN: A meta-analysis and a subgroup analysis were conducted. METHODS: English and Chinese databases including PubMed, Embase, CINAHL, Web of Science, Cochrane Library and China National Knowledge Infrastructure were searched for relevant articles published between the inception of these databases through May 2023. The search included the establishment of these databases up until May 2023. Using a search strategy, we identified 3273 potentially relevant articles. Ten primary studies were included in the final analysis. We used random effect models to synthesize effect size (ES) and accommodate heterogeneity for the main effect. Sub-group analyses were conducted to analyze the variations in effect size to investigate possible causes of heterogeneity. RESULTS: We found synchronous e-learning to be more effective compared with the control groups, with a pooled random-effects standardized mean difference of 0.51, which is a medium effect size. Regarding learning outcomes, the effect size of reactions to learning (ES = 0.91, confidence interval [CI] = 0.14, 1.67) was higher than that of the psychomotor domain (ES = 0.57, CI = 0.17, 0.98), cognitive domain (ES = 0.63, CI = 0.11, 1.15) and affective domain (ES = 0.40, CI = 0.03, 0.76). In terms of interaction types and study characteristics were more effective if the studies included learner-learner interaction (ES = 0.83, CI = 0.36, 1.29), developed regions (ES = 0.55, CI = 0.17, 0.94), undergraduate nursing students (ES = 0.56, CI = 0.32, 0.80), no randomization (ES = 0.75, CI = 0.40, 1.10) and funding support (ES = 0.78, CI = 0.41, 1.16). CONCLUSIONS: Well-designed synchronous e-learning courses should consider learners' motivations and self-directed learning abilities by providing diverse learning resources and environments. Nurse educators should develop synchronous e-learning teaching strategies that include peer interaction. The affective domain of learning in synchronous e-learning needs to be developed and considered in future research.

Dynamic analysis of acute deterioration in chronic liver disease patients using modified quick sequential organ failure assessment.

BACKGROUND/AIMS: Quick sequential organ failure assessment (qSOFA) is believed to identify patients at risk of poor outcomes in those with suspected infection. We aimed to evaluate the ability of modified qSOFA (m-qSOFA) to identify high-risk patients among those with acutely deteriorated chronic liver disease (CLD), especially those with acute-onchronic liver failure (ACLF). METHODS: We used data from both the Korean Acute-on-Chronic Liver Failure (KACLiF) and the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) cohorts. qSOFA was modified by replacing the Glasgow Coma Scale with hepatic encephalopathy, and an m-qSOFA ≥2 was considered high. RESULTS: Patients with high m-qSOFA had a significantly lower 1-month transplant-free survival (TFS) in both cohorts and higher organ failure development in KACLiF than those with low m-qSOFA (Ps<0.05). Subgroup analysis by ACLF showed that patients with high m-qSOFA had lower TFS than those with low m-qSOFA. m-qSOFA was an independent prognostic factor (hazard ratios, HR=2.604, 95% confidence interval, CI 1.353-5.013, P=0.004 in KACLiF and HR=1.904, 95% CI 1.484- 2.442, P<0.001 in AARC). The patients with low m-qSOFA at baseline but high m-qSOFA on day 7 had a significantly lower 1-month TFS than those with high m-qSOFA at baseline but low m-qSOFA on day 7 (52.6% vs. 89.4%, P<0.001 in KACLiF and 26.9% vs. 61.5%, P<0.001 in AARC). CONCLUSION: Baseline and dynamic changes in m-qSOFA may identify patients with a high risk of developing organ failure and short-term mortality among CLD patients with acute deterioration.

Twenty Years of Progress and the Way Forward: Immunization Registry Information System in Korea.

The National Immunization Program in The Republic of Korea offers mandatory and free vaccinations to children under 12, regulated by the Infectious Disease Prevention and Control Act. Tracking vaccination coverage is crucial for population protection and public health strategies. Since 2002, the Immunization Registry Information System (IRIS) has been used nationwide to capture vaccination data. This study reviewed documents related to IRIS's establishment and development. The Republic of Korea legally supports IRIS's construction and data collection, integrating vaccination data with the Ministry of the Interior and Safety's resident registration to minimize errors. This collaboration also facilitates cost reimbursement and digital registration, promoting wider vaccination coverage. IRIS manages expense claims once vaccination details are logged, and authorized medical institutions can access these records in real-time. Since 2015, the Korea Disease Control and Prevention Agency has been compiling annual data on national vaccination coverage. IRIS also sends automated reminders in 12 languages, reports adverse effects, and issues vaccination certificates. However, IRIS lacks integration between vaccine and disease registries, unlike countries such as England, Denmark, and the Netherlands. Improving integration capabilities could enhance IRIS's support for public health through an integrated information system.

The experience of good mentoring focused on overcoming turnover intention among millennial nurses.

Introduction: Millennials are emerging as a prominent demographic in the nursing workforce. It is necessary to create an environment that harmonizes the advantages of each generation in a nursing workforce in which various generations coexist. As the importance of mentoring programs for millennial nurses grows, it is believed that the effectiveness of mentoring to support millennial nurses can be enhanced by identifying the attributes of good mentors as perceived by nurses. This study aimed to explore the attributes of good mentors according to millennial nurses in the nursing workforce with a focus on overcoming turnover intention problems. Methods: Four focus group interviews were conducted to collect data, which were subsequently analyzed using Braun and Clarke's thematic analysis method. A descriptive qualitative design involving 22 millennial nurses employed at a tertiary hospital, Hospital A, in Seoul, Republic of Korea was utilized. Results and discussion: Four themes emerged from the analysis: the concept of a significant others, the presence of a driving force to endure, the importance of a guide to a harmonious life, and the value of a partner for growth. The participants themselves identified these themes. To prevent turnover intention among millennial nurses, mentors should employ diverse strategies, and institutional supports are crucial. Furthermore, since it is unrealistic to expect all ideal mentor characteristics to be present in one person, mentor development education is also necessary. This information is valuable for designing mentor development programs and for establishing a solid framework for effective mentoring programs.

Lagerstroemia macrocarpa extract inhibits Th2-mediated STAT6 signaling pathway in human keratinocytes.

In this study, we examined physiological functions as a key material to develop cosmeceuticals using extracts of Lagerstroemia macrocarpa Wall. Ex Kurz (L. macrocarpa). Initially, the L. macrocarpa extract was treated by different concentration and antioxidant assay (DPPH and ABTS) were performed to measure free radical scavenging ability. In the cytotoxicity experiment, the extract was treated into human epidermal keratinocytes with different concentrations to measure cytotoxicity. We found that the extract induces differentiation markers such as keratin (KRT)1, KRT2, KRT9, KRT10 in keratinocytes. Furthermore, the extract significantly induces involucrin (IVL), loricrin (LOR), claudin1 (CLDN1), and filaggrin (FLG) expression, suggesting that it may enhance skin barrier functions. Especially, the extract restored FLG expression inhibited by interleukin (IL)-4/IL-13 in in vitro atopic dermatitis-like model. Therefore, we expect L. macrocarpa extract will be an effective material to develop the therapeutic and cosmeceutical of atopic dermatitis.

Associations of anxiety and fatigue with hazardous occupational conditions of Korean nurses in early pregnancy: A cross-sectional study.

AIM: To identify occupational conditions associated with anxiety and fatigue among Korean nurses in early pregnancy. BACKGROUND: Pregnant nurses, like non-pregnant hospital nurses, are exposed to dangerous and stressful work environments, which can affect fatigue and anxiety. DESIGN AND METHODS: This cross-sectional study enrolled 1490 nurses who participated in the early pregnancy module in the Korea Nurses' Health Study between 2014 and 2020. Hierarchical linear regression analyses were employed to identify the factors associated with anxiety and fatigue among nurses in early pregnancy. RESULTS: One-fifth of participants were working night shifts, and more than two-thirds were working overtime. When using antineoplastic drugs and disinfectants, the rate of use of protective equipment varied depending on the size of the hospital. Working overtime and lifting heavy objects were associated with increased anxiety and fatigue among nurses. CONCLUSION: Overtime work was associated with both anxiety and fatigue among pregnant nurses. Pregnant hospital nurses were exposed to both night shift and overtime work. Therefore, hospital managers should improve hazardous working environments to protect the health of nurses in early pregnancy and their fetuses.

Development of an Acute Pain Assessment Tool for Patients in Post-anesthesia Care Units.

BACKGROUND: Post-operative pain is a common form of acute pain. Objective pain assessment in post-anesthesia care units after surgery is useful regardless of the patient's condition. AIMS: This study aimed to develop and evaluate an acute pain assessment tool for patients in post-anesthesia care units. DESIGN: This was a cross-sectional observational study comprising two stages: scale development and psychometric evaluation. SETTINGS:  . PARTICIPANTS/SUBJECTS:  . METHODS: Scale items were developed based on a literature review and content validity by experts. The validity and interrater reliability of the pain scale were evaluated using data from 218 patients admitted to the post-anesthesia care unit at a university hospital. A receiver operating characteristic curve was used to identify the sensitivity and specificity for determining the cutoff point for acute pain. RESULTS: We developed an objective acute pain scale, called the APA5, which ranges from 0-10 and comprises behavioral (facial and verbal expressions and body movement) and physiological (changes in heart rate and blood pressure) responses. The APA5 is valid and reliable for assessing acute pain in the recovery room. Sensitivity and specificity were acceptable when the cutoff was 2 out of 10 points. CONCLUSIONS: The APA5 is an easy and simple tool for measuring pain in patients in post-anesthesia care units who have difficulties with self-reporting.

Validity and reliability of the Korean version of the gender-friendliness barriers in nursing programs scale.

Introduction: The gender-friendliness barriers in nursing programs (GFB-NP) were used to measure perceived gender affinity among male nursing students in nursing education programs. Originally developed in Taiwan, this scale has not been used in Korea. The purpose of this study is to confirm the reliability and validity of the GFB-NP scale for Korean male nursing students. Methods: A convenience sample of male nursing students enrolled in the 1st to 4th year of nursing departments at five four-year universities located in three cities in Korea was used in the study. To confirm the validity and factor structure of the scale, both exploratory factor analysis and confirmatory factor analysis were employed. Results: The results support a four-factor structure: Professional acquisition opportunity, peer interaction, sociocultural prejudice, and gender role attitude. We confirmed that the Korean version of the GFB-NP is an appropriate tool for measuring the gender-friendliness educational environment perceived by male nursing students in nursing education. Discussion: The GFB-NP will serve as a framework for developing counseling and management strategies to help male nursing students successfully adapt to school life within the nursing education curriculum. Research with a longitudinal study design is recommended to investigate the progression of school adaptation through undergraduate program courses.

Quality assessment of systematic reviews with meta-analysis in undergraduate nursing education.

BACKGROUND: Little attention has been given to the methodological quality of meta-analyses in nursing education. This warrants further improvements in meta-analyses in nursing education. OBJECTIVE: This study aimed to assess the methodological quality of meta-analysis in the field of undergraduate nursing education. DESIGN: This was a methodological study to review the methodological quality of systematic reviews (SRs) with meta-analysis. METHODS: Exhaustive literature searches were performed using five comprehensive databases. Between 1994 and 2022, 11,827 studies were identified, and 41 full-text articles met the inclusion criteria. Two researchers extracted data using A Measurement Tool to Assess Systematic Reviews (AMSTAR)-2. The Chi-square test was conducted to make comparisons before and after 2017, the year AMSTAR-2 was released. RESULTS: A comprehensive literature retrieval strategy, inclusion and exclusion criteria, literature selection, and data extraction were observed in nursing education more than in other disciplines. Improvements to be made include pre-specifying the protocol, providing a list of excluded studies with their exclusion reasons, reporting the source of funding for the included studies, assessing and discussing the potential impact of risk of bias, as well as investigating and discussing publication bias and its impact. CONCLUSIONS: The number of SRs with meta-analyses in nursing education is increasing. This warrants efforts to improve the quality of research. In addition, guidelines for reporting SRs in the field of nursing education should be constantly updated.

Development of a scintillator-based optical soft x-ray (OSXR) diagnostic system for KSTAR tokamak.

We have developed a new scintillator-based optical soft x-ray (OSXR) diagnostic system for KSTAR. By utilizing fiber optic faceplates, mm-size lens arrays, and fiber bundles, we have successfully constructed a novel optical system for scintillator-based soft x-ray detection to overcome the limited vacuum-port conditions in KSTAR. P47 (Y2SiO5), which has a fast rise (∼7 ns) and decay (∼100 ns) time sufficient for detecting plasma instabilities observed in the kHz-MHz spectral range, was selected as the scintillator material for the KSTAR OSXR system. Scintillation toward each detection channel is collected by the lens arrays coupled to optical fiber cores, which are connected to the photodetector system. Initial results obtained during the 2022 KSTAR experimental campaign support the validity of the OSXR data through the consistency of OSXR measurement results with other diagnostics. We also observe that the OSXR system can capture magnetohydrodynamic activities, such as sawtooth oscillations, and provide valuable information for disruption mitigation studies using shattered pellet injection.

Patient safety interprofessional education program using medical error scenarios for undergraduate nursing and medical students in Korea.

Interprofessional education (IPE) for patient safety is becoming increasingly important worldwide. However, Korea lacks a systematic approach toward patient safety, despite the high demand for teamwork and patient communication education. This study aims to determine the effectiveness of a patient safety IPE program using medical error scenarios. The program was developed to enhance patient safety motivation and interprofessional learning attitudes among medical and nursing students, and evaluate the design of the program and students' satisfaction levels. The program comprises two modules, each consisting of lectures, team-based case analysis, role-play, and high-fidelity simulation activities. This study followed a quasi-experimental pre-post test design to determine program outcomes. An online survey for the Readiness for Interprofessional Learning Scale (RIPLS), patient safety motivation, program design evaluation, and program satisfaction was conducted before and after the program. Data were analyzed using descriptive statistics, paired sample t-tests, and Pearson's correlation. The pre-post RIPLS and patient safety results were significant (t = -5.21, p < .001;t = -3.20, p = .002). The results of the medical scenario examination of the patient safety IPE program showed improved motivation for patient safety among students, and contributed to the improvement of IPE learning attitudes by improving team work and collaboration.

Serum S100B Levels in Patients with Liver Cirrhosis and Hepatic Encephalopathy.

Hepatic encephalopathy (HE) is one of the main complications of liver cirrhosis (LC) and is classified into minimal hepatic encephalopathy (MHE) and overt hepatic encephalopathy (overt HE). S100B is expressed mainly in astrocytes and other glial cells, and S100B has been reported to be associated with various neurological disorders. The present study aimed to investigate the diagnostic ability of serum S100B to discriminate the grade of HE and the parameters correlated with serum S100B levels. Additionally, we investigated whether serum S100B levels can be used to predict 1-year mortality in cirrhotic patients. In total, 95 cirrhotic patients were consecutively enrolled and divided into the following three groups: (i) without any types of HEs; (ii) with MHE; and (iii) with overt HE. The diagnosis of MHE was made by the Mini-Mental State Examination (MMSE) and Psychometric Hepatic Encephalopathy Score (PHES). Among the three groups, there were no significant differences in serum S100B levels regardless of HE severity. The clinical parameters correlated with serum S100B levels were age, serum bilirubin, and creatinine levels. The Model for End-Stage Liver Disease (MELD) score showed a significant positive correlation with serum S100B levels. The relationship between serum S100B levels and MELD score was maintained in 48 patients without any type of HE. Additionally, hyperammonemia, low cholesterol levels, and the combination of serum S100B levels ≥ 35 pg/mL with MELD score ≥ 13 were factors for predicting 1- year mortality. In conclusion, serum S100B level was not useful for differentiating the severity of HE. However, we found that serum S100B levels can be affected by age, serum bilirubin, and creatinine in cirrhotic patients and are associated with MELD scores. Additionally, serum S100B levels showed the possibility of predicting 1-year mortality in cirrhotic patients. These findings suggest that serum S100B levels may reflect liver dysfunction and prognosis in liver disease.

Quercetin Attenuates the Production of Pro-Inflammatory Cytokines in H292 Human Lung Epithelial Cells Infected with Pseudomonas aeruginosa by Modulating ExoS Production.

The type three secretion system (T3SS) is a major virulence system of Pseudomonas aeruginosa (P. aeruginosa). The effector protein Exotoxin S (ExoS) produced by P. aeruginosa is secreted into the host cells via the T3SS. For the purpose of an experiment on inhibitors with regard to ExoS secretion, we developed a sandwich-type enzyme-linked immunosorbent assay (ELISA) system. Quercetin was selected because it has a prominent ExoS inhibition effect and also is known to have anti-inflammatory and antioxidant effects on mammalian cells. In this study, we investigated the effects of quercetin on the expression and secretion of ExoS using ELISA and Western blot analysis methods. The results showed that the secretion of ExoS was significantly decreased by 10 and 20 µM of quercetin. Also, popB, popD, pscF, and pcrV which are composed of the T3SS needle, are reduced by quercetin at the mRNA level. We also confirmed the inhibitory effect of quercetin on cytokines (IL-6, IL-1ß, and IL-18) in P. aeruginosa-infected H292 cells by real-time polymerase chain reaction (PCR) and ELISA. Collectively, quercetin inhibits the secretion of ExoS by reducing both ExoS production and the expression of the needle protein of T3SS. Furthermore, these results suggest that quercetin has the potential to be used as an anti-toxic treatment for the inflammatory disease caused by P. aeruginosa infection.

The SpACE-CCM: A facile and versatile cell culture medium-based biosensor for detection of SARS-CoV-2 spike-ACE2 interaction.

The COVID-19 pandemic is an ongoing global public health threat. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and binding of the SARS-CoV-2 spike to its receptor, angiotensin-converting enzyme 2 (ACE2), on host cells is critical for viral infection. Here, we developed a luminescent biosensor that readily detects interactions of the spike receptor-binding domain (RBD) and ACE2 in cell culture medium ('SpACE-CCM'), which was based on bimolecular complementation of the split nanoluciferase-fused spike RBD and ectodomain of ACE2 and further engineered to be efficiently secreted from cells by adding a heterologous secretory signal peptide (SSP). Screening of various SSPs identified 'interferon-α+alanine-aspartate' as the SSP that induced the highest activity. The SpACE-CCM biosensor was validated by observing a marked reduction of the activity caused by interaction-defective mutations or in the presence of neutralizing antibodies, recombinant decoy proteins, or peptides. Importantly, the SpACE-CCM biosensor responded well in assay-validating conditions compared with conventional cell lysate-based NanoLuc Binary Technology, indicating its advantage. We further demonstrated the biosensor's versatility by quantitatively detecting neutralizing activity in blood samples from COVID-19 patients and vaccinated individuals, discovering a small molecule interfering with the spike RBD-ACE2 interaction through high-throughput screening, and assessing the cross-reactivity of neutralizing antibodies against SARS-CoV-2 variants. Because the SpACE-CCM is a facile and rapid one-step reaction biosensor that aptly recapitulates the native spike-ACE2 interaction, it would be advantageous in many experimental and clinical applications associated with this interaction.

A Double-Blind, Randomized, Placebo-Controlled, Phase II Clinical Study To Evaluate the Efficacy and Safety of Camostat Mesylate (DWJ1248) in Adult Patients with Mild to Moderate COVID-19.

Although several antiviral agents have become available for coronavirus disease 2019 (COVID-19) treatment, oral drugs are still limited. Camostat mesylate, an orally bioavailable serine protease inhibitor, has been used to treat chronic pancreatitis in South Korea, and it has an in vitro inhibitory potential against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study was a double-blind, randomized, placebo-controlled, multicenter, phase 2 clinical trial in mild to moderate COVID-19 patients. We randomly assigned patients to receive either camostat mesylate (DWJ1248) or placebo orally for 14 days. The primary endpoint was time to clinical improvement of subject symptoms within 14 days, measured using a subjective 4-point Likert scale. Three hundred forty-two patients were randomized. The primary endpoint was nonsignificant, where the median times to clinical improvement were 7 and 8 days in the camostat mesylate group and the placebo group, respectively (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 0.84 to 1.43; P = 0.50). A post hoc analysis showed that the difference was greatest at day 7, without reaching significance. In the high-risk group, the proportions of patients with clinical improvement up to 7 days were 45.8% (50/109) in the camostat group and 38.4% (40/104) in the placebo group (odds ratio [OR] = 1.33; 95% CI, 0.77 to 2.31; P = 0.31); the ordinal scale score at day 7 improved in 20.0% (18/90) of the camostat group and 13.3% (12/90) of the placebo group (OR = 1.68; 95% CI, 0.75 to 3.78; P = 0.21). Adverse events were similar in the two groups. Camostat mesylate was safe in the treatment of COVID-19. Although this study did not show clinical benefit in patients with mild to moderate COVID-19, further clinical studies for high-risk patients are needed. (This trial was registered with ClinicalTrials.gov under registration no. NCT04521296).